TY - JOUR T1 - Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights JF - bioRxiv DO - 10.1101/067355 SP - 067355 AU - Alexander Gusev AU - Nick Mancuso AU - Hilary K Finucane AU - Yakir Reshef AU - Lingyun Song AU - Alexias Safi AU - Edwin Oh AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium AU - Steven McCarroll AU - Benjamin Neale AU - Roel Ophoff AU - Michael C O’Donovan AU - Nicholas Katsanis AU - Gregory E Crawford AU - Patrick F Sullivan AU - Bogdan Pasaniuc AU - Alkes L Price Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/08/02/067355.abstract N2 - Genome-wide association studies (GWAS) have identified over 100 risk loci for schizophrenia, but the causal mechanisms remain largely unknown. We performed a transcriptome-wide association study (TWAS) integrating expression data from brain, blood, and adipose tissues across 3,693 individuals with schizophrenia GWAS of 79,845 individuals from the Psychiatric Genomics Consortium. We identified 157 genes with a transcriptome-wide significant association, of which 35 did not overlap a known GWAS locus; the largest number involved alternative splicing in brain. 42/157 genes were also associated to specific chromatin phenotypes measured in 121 independent samples (a 4-fold enrichment over background genes). This high-throughput connection of GWAS findings to specific genes, tissues, and regulatory mechanisms is an essential step toward understanding the biology of schizophrenia and moving towards therapeutic interventions. ER -